Nutritional compositions with lipid globules with a core comprising vegetable lipids and a coating comprising phospholipids or polar lipids

ABSTRACT

The present invention relates to a nutritional composition for infants and/or toddlers comprising a lipid component which has a large lipid globule size. The composition can be used to prevent obesity and/or improve body composition later in life. Said lipid component comprises 10-50 wt % vegetable lipids, and the lipid globules have a volume-weighted diameter above 1.0 m and/or a diameter of 2-12 m in an amount of at least 45 vol %.

FIELD OF THE INVENTION

The invention relates to the field of infant milk formula and growing upmilks for preventing obesity later in life.

BACKGROUND

Breast-feeding is the preferred method of feeding infants. However,there are circumstances that make breast-feeding impossible or lessdesirable. In those cases infant formulae are a good alternative. Thecomposition of modern infant formulae is adapted in such a way that itmeets many of the special nutritional requirements of the fast growingand developing infant.

Still it seems that improvements can be made towards the constitution ofinfant milk formulae. Breast fed infants have a decreased chance ofbecoming obese later in life, compared to formula fed infants, butlittle is known about the effects of ingredients in the infant formulaeon obesity later in life. So far, most research is dedicated to the roleof protein concentration or of the fatty acid composition. Obesity is amajor health problem in the Western world. It is a medical condition inwhich excess has accumulated to the extent that it may have an adverseeffect on health, leading to reduced life expectancy and it isassociated with many diseases, particularly heart disease and type 2diabetes. Obesity is a leading preventable cause of death worldwide,with increasing prevalence in adults and children, and authorities viewit as one of the most serious public health problems of the 21stcentury.

The present invention relates to such future healthy body composition.

WO 2007/073194 relates to infant formulae comprising phospholipids,sphingolipids, and cholesterols for the prevention of obesity. WO2007/073193 relates to infant formulae with specific linoleic acid toalpha-linolenic acid ratio's, low linoleic acid content and comprisingphospholipids, sphingolipids, cholesterol and/or choline plus uridinefor the prevention of obesity later in life. EP1800675 relates to acomposition with polyunsaturated fatty acids, proteins and manganeseand/or molybdene for improving membrane composition for the treatment ofa wide variety of disorders.

Michalski et al, 2005, J Dairy Sci 88:1927-1940 discloses the sizedistribution of lipid globules in human milk and infant formula. WO2005/051091 relates to a lipid combination which upon dispersion oremulsification in an essentially aqueous medium with other ingredientsof infant formula forms a substantially homogenous dispersion oremulsion having a lipid globule-containing microstructure which isessentially mimetic of the corresponding globular microstructure ofnaturally occurring HMF. SU 1084006 discloses food for children andinvalid people with a lipid globule size of 4 μM diameter, similar tohuman milk.

SUMMARY OF THE INVENTION

The inventors surprisingly found that the lipid globule size in infantformulae affects the body composition later in life. Specific selectionof the lipid globule size in infant formulae results in a decreased fatmass and/or decreased obesity later in life. Specific selection of thelipid globule size in infant formulae also resulted in an increased leanbody mass later in life. When early in life an infant formula of thepresent invention that comprised lipids with a larger lipid globule sizethan present in conventional infant formulae, was administered, it wasobserved that later in life the body composition was changed, resultingin less fat mass and less fat mass relative to total body weight and anincreased lean body mass compared to the body composition uponadministering conventional infant formula. In particular the visceralobesity, which is most associated with health problems, was reduced. Inparticular the adipocte hypertrophy was reduced. Obesity caused byadipocyte hypertrophy is thought to be indicative for onset of obesitylater in life and is more associated with health problems such asinsulin resistance than obesity caused by adipocyte hyperplasia.

The important difference between the investigated formulae was the sizeof the lipid globules, whereas the fatty acid profile was similar in theformulae.

The investigated formulae further enabled a similar good growth anddevelopment early in life and more particularly had no effect on fatmass early in life. So there was no direct effect, e.g. an obesitypreventive effect, of the diet. This is advantageous since in infantsand young children fat mass has important roles in energy storage,insulation, storage of fat soluble vitamins and hormonal development,such as the development of leptin and insulin sensitivity and it istherefore not desired to decrease fat mass in infants and youngchildren.

An even improved effect on fat mass, and fat mass relative to total bodymass later in life was observed when the large lipid globules werecoated by an outer layer of polar lipids. This improvement could not beexplained by the presence of the polar lipids itself, since mereaddition of polar lipids without coating of the lipid globules did notshow these improved effects.

Standard infant milk formulae have vegetable fat as lipid component. Thelipid is homogenized in order to create a stable emulsion and the lipidglobules are small, with a volume-weighted mode diameter of about0.3-0.6 μm. Less than 55 volume % based on total lipid, typically lessthan 35 vol. %, has a size between 2 and 12 μm. The lipid globules arefor a large part covered with milk proteins, in particular casein.

The present invention relates to infant formulae or growing up milks fortoddlers comprising vegetable fats with a lipid globule size larger thanthat of standard infant formulae. The present composition compriseslipid globules with a lipid volume-weighted mode diameter of above 1.0μm, preferably between 1.0 and 10 μm, and/or with at least 45, morepreferably at least 55 volume % with a diameter of 2 to 12 μm based ontotal lipid. This can be achieved upon homogenizing of the lipidcomponent comprising vegetable fat at lower pressures, preferably in thepresence of polar lipids in order to coat the enlarged lipid globulesand make them more stable. It was found that the thus obtained oil inwater emulsion is stable for at least 48 h. Especially when the formulaeis dried to a powder and subsequently reconstituted with water to aready to drink formula shortly before use, no disadvantageous effectsregarding stability are observed.

It has now surprisingly been found that the size of the lipid globuleadministered early in life is one of the determining factors whichaffect body composition, in particular fat mass, more particularvisceral fat mass, and lean body mass, later in life. This effect on fatmass was even more pronounced when the large lipid globules were coatedwith polar lipids such as phospholipids. Since advantageously no acuteeffects of the diet on body composition were observed, it is concludedthat the diet programmed or imprinted the body in such a way that itresulted in the development of an improved body composition later inlife after further growth under similar conditions.

The present invention therefore can be used for food compositionsintended for infants and/or toddlers in order to prevent obesity,visceral obesity, increase lean body mass and/or decrease fat mass laterin life.

DETAILED DESCRIPTION

The present invention thus concerns a method for prevention of obesity,reducing the risk of obesity, and/or treatment of obesity, said methodcomprising administering to a human subject a nutritional compositioncomprising

a) 10 to 50 wt. % vegetable lipids based on dry weight of thecomposition, and

b) lipid globules

-   -   i) with a volume-weighted mode diameter above 1.0 μm, preferably        between 1.0 and 10 μm, and/or    -   ii) with a diameter of 2 to 12 μm in an amount of at least 45,        more preferably at least 55 volume % based on total lipid.

For sake of clarity it is noted that the lipid globules as defined underb) comprise vegetable lipids as defined under a) or in other words thata) and b) overlap.

Also the present invention concerns a method for improving bodycomposition, the improvement of body composition being selected from thegroup consisting of increased lean body mass, decreased fat mass, anddecreased relative fat mass, said method comprising administering to ahuman subject a nutritional composition comprising

a) 10 to 50 wt. % vegetable lipids based on dry weight of thecomposition, and

b) lipid globules

-   -   i) with a volume-weighted mode diameter above 1.0 μm, preferably        between 1.0 and 10 μm, and/or    -   ii) with a diameter of 2 to 12 μm in an amount of at least 45,        more preferably at least 55 volume % based on total lipid.

In one aspect the present invention relates to a non-therapeutic methodfor prevention of obesity and/or reducing the risk of obesity, saidmethod comprising administering to a human subject a nutritionalcomposition comprising

a) 10 to 50 wt. % vegetable lipids based on dry weight of thecomposition, and

b) lipid globules

-   -   i) with a volume-weighted mode diameter above 1.0 μm, preferably        between 1.0 and 10 μm, and/or    -   ii) with a diameter of 2 to 12 μm in an amount of at least 45,        more preferably at least 55 volume % based on total lipid.

Also in a further aspect the present invention relates to anon-therapeutic method for improving body composition, the improvementof body composition being selected from the group consisting ofincreased lean body mass, decreased fat mass, and decreased relative fatmass, said method comprising administering to a human subject anutritional composition comprising

a) 10 to 50 wt. % vegetable lipids based on dry weight of thecomposition, and

b) lipid globules

-   -   i) with a volume-weighted mode diameter above 1.0 μm, preferably        between 1.0 and 10 μm, and/or    -   ii) with a diameter of 2 to 12 μm in an amount of at least 45,        more preferably at least 55 volume % based on total lipid.

The present invention can also be worded as the use of lipid for themanufacture of a nutritional composition for prevention of obesity,reducing the risk of obesity, and/or treatment of obesity, saidnutritional composition comprising

a) 10 to 50 wt. % vegetable lipids based on dry weight of thecomposition, and

b) lipid globules

-   -   i) with a volume-weighted mode diameter above 1.0 μm, preferably        between 1.0 and 10 μm, and/or    -   ii) with a diameter of 2 to 12 μm in an amount of at least 45,        more preferably at least 55 volume % based on total lipid.

The invention also concerns the use of lipid for the manufacture of anutritional composition for improving body composition, the improvementof body composition being selected from the group consisting ofincreased lean body mass, decreased fat mass, and decreased relative fatmass, said nutritional composition comprising

a) 10 to 50 wt. % vegetable lipids based on dry weight of thecomposition, and

b) lipid globules

-   -   i) with a volume-weighted mode diameter above 1.0 μm, preferably        between 1.0 and 10 μm, and/or    -   ii) with a diameter of 2 to 12 μm in an amount of at least 45,        more preferably at least 55 volume % based on total lipid.

The present invention can also be worded as a nutritional compositioncomprising

a) 10 to 50 wt. % vegetable lipids based on dry weight of thecomposition, and

b) lipid globules

-   -   i) with a volume-weighted mode diameter above 1.0 μm, preferably        between 1.0 and 10 μm, and/or    -   ii) with a diameter of 2 to 12 μm in an amount of at least 45,        more preferably at least 55 volume % based on total lipid.        for use in prevention of obesity, reducing the risk of obesity,        and/or treatment of obesity.

The invention also concerns a nutritional composition comprising

a) 10 to 50 wt. % vegetable lipids based on dry weight of thecomposition, and

b) lipid globules

-   -   i) with a volume-weighted mode diameter above 1.0 μm, preferably        between 1.0 and 10 μm, and/or    -   ii) with a diameter of 2 to 12 μm in an amount of at least 45,        more preferably at least 55 volume % based on total lipid        for use in improving body composition, the improvement of body        composition being selected from the group consisting of        increased lean body mass, decreased fat mass, and decreased        relative fat mass.

Further the invention relates to a nutritional composition comprising

-   -   a) 10 to 50 wt. % vegetable lipids based on dry weight of the        composition, and    -   b) lipid globules        -   i) with a volume-weighted mode diameter above 1.0 μm,            preferably between 1.0 and 10 μm, and/or        -   ii) with a diameter of 2 to 12 μm in an amount of at least            45 volume %, more preferably at least 55 volume % based on            total lipid, and    -   c) 0.5-20 wt. % phospholipids based on total lipid, wherein the        phospholipids are derived from milk lipids.

Further the invention relates to a nutritional composition comprising

-   -   a) 10 to 50 wt. % vegetable lipids based on dry weight of the        composition, and    -   b) lipid globules        -   i) with a volume-weighted mode diameter above 1.0 μm,            preferably between 1.0 and 10 μm, and/or        -   ii) with a diameter of 2 to 12 μm in an amount of at least            45 volume %, more preferably at least 55 volume % based on            total lipid, and    -   c) 0.6 to 25 wt. % of polar lipids based on total lipids,        wherein polar lipids are the sum of phospholipids,        glycosphingolipids and cholesterol based on total lipid.

Also the invention relates to a process for making a nutritionalcomposition comprising the steps of

-   -   a) providing an aqueous mixture comprising lipids, wherein the        lipids comprise 50 to 100 wt. % vegetable lipid based on total        lipid and wherein 0.2 to 20 wt. % based on total lipid is        phospholipid, and comprising protein, digestible carbohydrate,        and optionally non-digestible oligosaccharide, and    -   b) homogenizing said mixture in two steps with 5-100 bar,        preferably 30-100 bar in the first step and 5-50 bar in the        second step, and    -   c) preferably sterilizing said homogenized mixture and    -   d) preferably spray drying said sterilized mixture.

A sterilization step can also be performed prior to step b). In thiscase step c) preferably is omitted. Thus in one embodiment the processaccording to the invention comprises a step al) of sterilizing theaqueous mixture obtained in step a).

Obesity

The present composition is preferably administered to a human subjectwith an age below 36 months, preferably below 18 months, more preferablybelow 12 months, even more preferably below 6 months. Preferably thehuman subject is not obese and/or not suffering from overweight.

Obesity in the present invention relates to an excess of body fat mass.Fat mass is also known as adipose tissue or fat tissue. An adult humanperson suffers from obesity if over 25 wt. % (for man) or over 30 wt. %(for women) of body weight is fat mass. Obesity is sometimes referred toas adiposity.

Suitable ways to determine % body fat mass are underwater weighing, skinfold measurement, bioelectrical impedance analysis, computed tomography(CT/CAT scan), magnetic resonance imaging (MRI/NMR), ultrasonography anddual energy X-ray absorptiometry (DEXA). A preferred method is DEXAmeasurement. In the context of this invention body fat mass isdetermined by DEXA.

The increased risk of health problems later in life, such as diabetesand cardiovascular diseases, is related to the occurrence of visceraladiposity and not to general obesity. The term ‘visceral obesity’ refersto a condition with increased visceral fat tissue. Visceral adiposity istypically caused by (accumulation of) excessive visceral fat tissue.Visceral fat, also known as organ fat, intra-abdominal fat, peritonealfat or central fat, is normally located inside the peritoneal cavity asopposed to subcutaneous fat which is found underneath the skin andintramuscular fat which is found interspersed in skeletal muscles.Visceral fat includes the abdominal fat surrounding the vital organs andincludes mesenteric fat, perirenal fat, retroperitoneal fat andpreperitoneal fat (fat surrounding the liver). A waist circumferenceabove 102 cm in adult man or above 88 cm in adult women indicates thepresence of visceral adiposity. Hip-waist ratio's exceeding 0.9 in manand 0.85 in women indicate visceral adiposity. For children of 3-19years old appropriate cutoffs for age- and sex-dependent waistcircumferences can be found in Taylor et al, 2000 Am J Clin Nutr72:490-495. A subject suffers from visceral adiposity when it meets oneor more of the above criteria (regarding VAT, waist circumference orwaist-hip ratio thresholds).

Lipid Component

The present composition comprises lipid. The lipid provides preferably30 to 60% of the total calories of the composition. More preferably thepresent composition comprises lipid providing 35 to 55% of the totalcalories, even more preferably the present composition comprises lipidproviding 40 to 50% of the total calories. When in liquid form, e.g. asa ready-to-feed liquid, the composition preferably comprises 2.1 to 6.5g lipid per 100 ml, more preferably 3.0 to 4.0 g per 100 ml. Based ondry weight the present composition preferably comprises 10 to 50 wt. %,more preferably 12.5 to 40 wt. % lipid, even more preferably 19 to 30wt. % lipid.

Lipids include polar lipids (such as phospholipids, glycolipids,sphingomyelin, and cholesterol), monoglycerides, diglycerides,triglycerides and free fatty acids. Preferably the composition comprisesat least 75 wt. %, more preferably at least 85 wt. % triglycerides basedon total lipids.

The lipid of the present invention comprises vegetable lipids. Thepresence of vegetable lipids advantageously enables an optimal fattyacid profile, high in (poly)unsaturated fatty acids and/or morereminiscent to human milk fat. Using lipids from cow's milk alone, orother domestic mammals, does not provide an optimal fatty acid profile.This less optimal fatty acid profile, such as a large amount ofsaturated fatty acids, is known to result in increased obesity.Preferably the present composition comprises at least one, preferably atleast two lipid sources selected from the group consisting of linseedoil (flaxseed oil), rape seed oil (such as colza oil, low erucic acidrape seed oil and canola oil), salvia oil, perilla oil, purslane oil,lingonberry oil, sea buckthorn oil, hemp oil, sunflower oil, high oleicsunflower oil, safflower oil, high oleic safflower oil, olive oil, blackcurrant seed oil, echium oil, coconut oil, palm oil and palm kernel oil.Preferably the present composition comprises at least one, preferably atleast two lipid sources selected from the group consisting of linseedoil, canola oil, coconut oil, sunflower oil and high oleic sunfloweroil. Commercially available vegetable lipids are typically offered inthe form a continuous oil phase. When in liquid form, e.g. as aready-to-feed liquid, the composition preferably comprises 2.1 to 6.5 gvegetable lipid per 100 ml, more preferably 3.0 to 4.0 g per 100 ml.Based on dry weight the present composition preferably comprises 10 to50 wt. %, more preferably 12.5 to 40 wt. % vegetable lipid, even morepreferably 19 to 30 wt. %. Preferably the composition comprises 50 to100 wt. % vegetable lipids based on total lipids, more preferably 70 to100 wt. %, even more preferably 75 to 97 wt. %. It is noted thereforethat the present composition also may comprise non-vegetable lipids.Suitable and preferred non-vegetable lipids are further specified below.

Lipid Globule Size

According to the present invention, lipid is present in the compositionin the form of lipid globules, emulsified in the aqueous phase. Thelipid globules of the present invention have

-   -   1. a volume-weighted mode diameter above 1.0 μm, preferably        above 3.0 μm, more preferably 4.0 μm or above, preferably        between 1.0 and 10 μm, more preferably between 2.0 and 8.0 μm,        even more preferably between 3.0 and 8.0 μm, most preferably        between 4.0 and 8.0 μm and/or    -   2. a size distribution in such a way that at least 45 volume %,        preferably at least 55 volume %, even more preferably at least        65 volume %, even more preferably at least 75 volume % has a        diameter between 2 and 12 μm. More preferably at least 45 volume        %, preferably at least 55 volume %, even more preferably at        least 65 volume %, even more preferably at least 75 volume % has        a diameter between 2 and 10 μm. Even more preferably at least 45        volume %, preferably at least 55 volume %, even more preferably        at least 65 volume %, even more preferably at least 75 volume %        has a diameter between 4 and 10 μm.

The percentage of lipid globules is based on volume of total lipid. Themode diameter relates to the diameter which is the most present based onvolume of total lipid, or the peak value in a graphic representation,having on the X-as the diameter and on the Y-as the volume (%). Thevolume of the lipid globule and its size distribution can suitably bedetermined using a particle size analyzer such as a Mastersizer (MalvernInstruments, Malvern, UK), for example by the method described inMichalski et al, 2001, Lait 81: 787-796.

Polar Lipids

The present invention preferably comprises polar lipids. Polar lipidsare amphipathic of nature and include glycerophospholipids,glycosphingolipids, sphingomyelin and/or cholesterol. More preferablythe composition comprises phospholipids (the sum of glycerophospholipidsand sphingomyelin). Polar lipids in the present invention relate to thesum of glycerophospholipids, glycosphingolipids, sphingomyelin andcholesterol. Preferably the polar lipids are present as a coating orouter layer of the lipid globule. The presence of polar lipids as acoating or outer layer of the lipid globule was found to advantageouslyfurther decrease fat mass and relative fat mass, i.e. obesity. Thepresence of polar lipids helps to maintain the lipid globules emulsifiedin the aqueous composition. This is especially important when the lipidglobule size is large. Thus in one embodiment according to the presentinvention the lipid globules are coated with a layer of phospholipids orpolar lipids. Thus preferably the lipid globules comprise a core and acoating. The core comprises vegetable fat and preferably comprises atleast 90 wt. % triglycerides and more preferably essentially consists oftriglycerides. The coating comprises phospholipids and/or polar lipids.Not all phospholipids and/or polar lipids that are present in thecomposition need necessarily be comprised in the coating, but preferablya major part is. Preferably more than 50 wt. %, more preferably morethan 70 wt. %, even more preferably more than 85 wt. %, most preferablymore than 95 wt. % of the phospholipids and/or polar lipids that arepresent in the composition are comprised in the coating of lipidglobules. Not all vegetable lipids that are present in the compositionneed necessarily be comprised in the core of lipid globules, butpreferably a major part is, preferably more than 50% wt. %, morepreferably more than 70 wt. %, even more preferably more than 85 wt. %,even more preferably more than 95 wt. %, most preferably more than 98wt. % of the vegetable lipids that are present in the composition arecomprised in the core of lipid globules.

The present composition preferably comprises glycerophospholipids.Glycerophospholipids are a class of lipids formed from fatty acidsesterified at the hydroxyl groups on carbon-1 and carbon-2 of thebackbone glycerol moiety and a negatively-charged phosphate groupattached to carbon-3 of the glycerol via an ester bond, and optionally acholine group (in case of phosphatidylcholine, PC), a serine group (incase of phosphatidylserine, PS), an ethanolamine group (in case ofphosphatidylethanolamine, PE), an inositol group (in case ofphosphatidylinositol, PI) or a glycerol group (in case ofphosphatidylglycerol, PG) attached to the phosphate group.Lysophospholipids are a class of phospholipids with one fatty acylchain. Preferably the present composition contains PC, PS, PI and/or PE,more preferably at least PC. Preferably the glycerophospholipidscomprise negatively charged phospholipids in particular PS and/or PI.Negatively charged glycerophospholipids advantageously improve thestability of the oil in water emulsion.

The present composition preferably comprises glycosphingolipids. Theterm glycosphingolipids as in the present invention particularly refersto glycolipids with an amino alcohol sphingosine. The sphingosinebackbone is O-linked to a charged headgroup such as ethanolamine, serineor choline backbone. The backbone is also amide linked to a fatty acylgroup. Glycosphingolipids are ceramides with one or more sugar residuesjoined in a β-glycosidic linkage at the 1-hydroxyl position. Preferablythe present composition contains gangliosides, more preferably at leastone ganglioside selected from the group consisting of GM3 and GD3.

The present composition preferably comprises sphingomyelin.Sphingomyelins have a phosphorylcholine or phosphorylethanolaminemolecule esterified to the 1-hydroxy group of a ceramide. They areclassified as phospholipid as well as sphingolipid, but are notclassified as a glycerophospholipid nor as a glycosphingolipid.

Sphingolipids are in the present invention defined as the sum ofsphingomyelin and glycosphingolipids. Phospholipids are in the presentinvention defined as the sum of sphingomyelin and glycerophospholipids.Preferably the phospholipids are derived from milk lipids. Preferablythe weight ratio of phospholipids:glycosphingolipids is from 2:1 to10:1, more preferably 2:1 to 5:1.

Preferably the present composition comprises phospholipids. Preferablythe present composition comprises 0.2 to 20 wt. % phospholipids based ontotal lipid, more preferably 0.5 to 20 wt. % phospholipids based ontotal lipid, more preferably 0.5 to 10 wt. %, more preferably 1 to 10wt. %, even more preferably 3 to 8 wt. %. Preferably the presentcomposition comprises 0.1 to 10 wt. % glycosphingolipids based on totallipid, more preferably 0.5 to 5 wt. %, even more preferably 2 to 4 wt %.Preferably the present composition comprises 0.3 to 20 wt. %(glycosphingolipids plus phospholipids) based on total lipid, morepreferably 0.5 to 20 wt. % (glycosphingolipids plus phospholipids) basedon total lipid, more preferably 1 to 10 wt. %.

The present composition preferably comprises cholesterol. The presentcomposition preferably comprises at least 0.005 wt. % cholesterol basedon total lipid, more preferably at least 0.02 wt. %, more preferably atleast 0.05 wt. %., even more preferably at least 0.1 wt. %. Preferablythe amount of cholesterol does not exceed 10 wt. % based on total lipid,more preferably does not exceed 5 wt. %, even more preferably does notexceed 1 wt. % of total lipid.

Preferably the present composition comprises 0.3 to 25 wt. % polarlipids based on total lipid, wherein the polar lipids are the sum ofphospholipids, glycosphingolipids, and cholesterol, more preferably 0.6to 25 wt. % polar lipids based on total lipid, more preferably 0.6 to 12wt. %, more preferably 1 to 10 wt. %, even more preferably 3 to 10 wt.%.

Preferred sources for providing the phospholipids, glycosphingolipidsand/or cholesterol are egg lipids, milk fat, buttermilk fat and butterserum fat (such as beta serum fat). A preferred source forphospholipids, particularly PC, is soy lecithin and/or sunflowerlecithin. The present composition preferably comprises phospholipidsderived from milk. Preferably the present composition comprisesphospholipids and glycosphingolipids derived from milk. Preferably alsocholesterol is obtained from milk. Preferably the polar lipids arederived from milk. Polar lipids derived from milk include the polarlipids isolated from milk lipid, cream lipid, butter serum lipid (betaserum lipid), whey lipid, cheese lipid and/or buttermilk lipid. Thebuttermilk lipid is typically obtained during the manufacture ofbuttermilk. The butter serum lipid or beta serum lipid is typicallyobtained during the manufacture of anhydrous milk fat from butter.Preferably the phospholipids, glycosphingolipids and/or cholesterol areobtained from milk cream. The composition preferably comprisesphospholipids, glycosphingolipids and/or cholesterol from milk of cows,mares, sheep, goats, buffalos, horses and camels. It is most preferredto use a lipid extract isolated from cow's milk. Polar lipids derivedfrom fat milk advantageously decrease fat mass to a larger extent thanpolar lipids from other sources. Preferably the polar lipids are locatedon the surface of the lipid globule, i.e. as a coating or outer layer. Asuitable way to determine whether the polar lipids are located on thesurface of the lipid globules is laser scanning microscopy as describedin example 1. The concomitant use of polar lipids derived from domesticanimals milk and trigycerides derived from vegetable lipids thereforeenables to manufacture lipid globules with an architecture more similarto human milk, while at the same time providing an optimal fatty acidprofile. Suitable commercially available sources for milk polar lipidsare BAEF, SM2, SM3 and SM4 powder of Corman, Salibra of Glanbia, andLacProdan MFGM-10 or PL20 from Arla. Preferably the source of milk polarlipids comprises at least 4 wt. % phospholipids based on total lipid,more preferably 7 to 75 wt. %, most preferably 20 to 70 wt. %phospholipids based on total lipid.

Preferably the weight ratio phospholipids to protein is above 0.10, morepreferably above 0.20, even more preferably above 0.3. Preferably atleast 25 wt. %, more preferably at least 40 wt. %, most preferably atleast 75 wt. % of the polar lipids is derived from milk polar lipids.

Fatty Acid Composition

Herein LA refers to linoleic acid and/or acyl chain (18:2 n6); ALArefers to α-linolenic acid and/or acyl chain (18:3 n3); LC-PUFA refersto long chain polyunsaturated fatty acids and/or acyl chains comprisingat least 20 carbon atoms in the fatty acyl chain and with 2 or moreunsaturated bonds; DHA refers to docosahexaenoic acid and/or acyl chain(22:6, n3); EPA refers to eicosapentaenoic acid and/or acyl chain (20:5n3); ARA refers to arachidonic acid and/or acyl chain (20:4 n6); DPArefers to docosapentaenoic acid and/or acyl chain (22:5 n3). Mediumchain fatty acids (MCFA) refer to fatty acids and/or acyl chains with achain length of 6, 8 or 10 carbon atoms.

LA preferably is present in a sufficient amount in order to promote ahealthy growth and development, yet in an amount as low as possible toprevent occurrence of obesity later in life. The composition thereforepreferably comprises less than 15 wt. % LA based on total fatty acids,preferably between 5 and 14.5 wt. %, more preferably between 6 and 10wt. %. Preferably the composition comprises over 5 wt. % LA based onfatty acids. Preferably ALA is present in a sufficient amount to promotea healthy growth and development of the infant. The present compositiontherefore preferably comprises at least 1.0 wt. % ALA based on totalfatty acids.

Preferably the composition comprises at least 1.5 wt. % ALA based ontotal fatty acids, more preferably at least 2.0 wt. %. Preferably thecomposition comprises less than 10 wt. % ALA, more preferably less than5.0 wt. % based on total fatty acids. The weight ratio LA/ALA should bewell balanced in order to prevent obesity, while at the same timeensuring a normal growth and development. Therefore, the presentcomposition preferably comprises a weight ratio of LA/ALA between 2 and15, more preferably between 2 and 7, more preferably between 4 and 7,more preferably between 3 and 6, even more preferably between 4 and 5.5,even more preferably between 4 and 5.

Since MCFA contribute to a reduced fat mass later in life whenadministered to an infant, the present composition preferably comprisesat least 3 wt. % MCFA based on total fatty acids, more preferably atleast 10 wt. %, even more preferably 15 wt. %. Since MCFA reduces bodyfat deposition with no preference for central fat mass, and since MFCAdoes not decrease the number of adipocytes, the present compositionadvantageously comprises less than 50 wt. % MCFA based on total fattyacids, more preferably less than 40 wt. %, even more preferably lessthan 25 wt. %.

Preferably the present composition comprises n-3 LC-PUFA, since n-3LC-PUFA reduce obesity later in life, more preferably central obesity.More preferably, the present composition comprises EPA, DPA and/or DHA,even more preferably DHA. Since a low concentration of DHA, DPA and/orEPA is already effective and normal growth and development areimportant, the content of n-3 LC-PUFA in the present composition,preferably does not exceed 15 wt. % of the total fatty acid content,preferably does not exceed 10 wt. %, even more preferably does notexceed 5 wt. %. Preferably the present composition comprises at least0.2 wt. %, preferably at least 0.5 wt. %, more preferably at least 0.75wt. %, n-3 LC-PUFA of the total fatty acid content.

As the group of n-6 fatty acids, especially arachidonic acid (AA) and LAas its precursor, counteracts the group of n-3 fatty acids, especiallyDHA and EPA and ALA as their precursor, the present compositioncomprises relatively low amounts of AA. The n-6 LC-PUFA contentpreferably does not exceed 5 wt. %, more preferably does not exceed 2.0wt. %, more preferably does not exceed 0.75 wt. %, even more preferablydoes not exceed 0.5 wt. %, based on total fatty acids. Since AA isimportant in infants for optimal functional membranes, especiallymembranes of neurological tissues, the amount of n-6 LC-PUFA ispreferably at least 0.02 wt. % more preferably at least 0.05 wt. %, morepreferably at least 0.1 wt. % based on total fatty acids, morepreferably at least 0.2 wt. %. The presence of AA is advantageous in acomposition low in LA since it remedies LA deficiency. The presence of,preferably low amounts, of AA is beneficial in nutrition to beadministered to infants below the age of 6 months, since for theseinfants the infant formulae is generally the only source of nutrition.

Preferably in addition to the vegetable lipid, a lipid selected fromfish oil (preferably tuna fish oil) and single cell oil (such as algal,microbial oil and fungal oil) is present. These sources of oil aresuitable as LC-PUFA sources. Preferably as a source of n-3 LC-PUFAsingle cell oil, including algal oil and microbial oil, is used, sincethese oil sources have a low EPA/DHA ratio, which results in anincreased anti-obesity effect. More preferably fish oil (even morepreferably tuna fish oil) is used as a source of n-3 LC-PUFA since theyhave a higher EPA concentration which is advantageous since EPA isprecursor of eicosanoids which have an additional anti-obesity effect.Thus in one embodiment the present composition further comprises atleast one lipid selected from the group consisting of fish oil, marineoil, algal oil, fungal oil and microbial oil.

Process for Obtaining Lipid Globules

The present composition comprises lipid globules. The lipid globule sizecan be manipulated by adjusting process steps by which the presentcomposition is manufactured. A suitable and preferred way to obtainlarger lipid globule sizes is to adapt the process of homogenization. Instandard infant milk formula the lipid fraction (usually comprisingvegetable fat, a small amount of polar lipids and fat soluble vitamins)is mixed into the aqueous fraction (usually comprising water, skimmedmilk, whey, digestible carbohydrates such as lactose, water solublevitamins and minerals and optionally non-digestible carbohydrates) byhomogenization. If no homogenization was to take place, the lipid partwould cream very quickly, i.e. separate from the aqueous part andcollect at the top. Homogenization is the process of breaking up the fatphase into smaller sizes so that it no longer quickly separates from theaqueous phase but is maintained in a stable emulsion. This isaccomplished by forcing the milk at high pressure through smallorifices.

However, the present inventors found that homogenization at a lowerpressure than usually applied in the preparation of infant formularesulted in the larger lipid globules of the present invention, whilemaintaining a sufficiently stable emulsion.

The process comprises the following steps:

1 Mixing Ingredients

The ingredients of the composition are mixed, e.g. preferably blended.Basically a lipid phase, comprising the vegetable lipids, and an aqueousphase are added together. The ingredients of the aqueous phase maycomprise water, skimmed milk (powder), whey (powder), low fat milk,lactose, water soluble vitamins and minerals. Preferably the aqueousphase comprises protein, digestible carbohydrates, and polar lipids,more preferably phospholipids. Preferably the aqueous phase comprisesnon-digestible oligosaccharides. Preferably the aqueous phase is set ata pH between 6.0 and 8.0, more preferably pH 6.5 to 7.5. Preferably thepolar lipids, in particular the phospholipids are derived from milk. Thepresence of polar lipids advantageously results in more stable lipidglobules. This is especially important in case of larger lipid globules.Advantageously, having polar lipids present in the aqueous mixturebefore homogenization results in coating of the lipid globules,consisting essentially of triglycerides, with a layer of polar lipids.

Preferably the lipid phase comprises 50 to 100 wt. % vegetable lipidsbased on total weight of the lipid phase. Instead of in the aqueousphase, the polar lipids, more preferably the phospholipids, may also bepresent in the lipid phase or in both phases. Alternatively the polarlipids may be added separately to an aqueous and lipid phase.Preferably, the weight ratio of phospholipid to total lipid is from 0.2to 20 wt. %, more preferably from 0.5 to 10 wt. %, even more preferably3 to 8 wt. % 0.2.

The aqueous and lipid phase are preferably heated before addingtogether, preferably at a temperature of 40° C. to 80° C., morepreferably 55° C. to 70° C., even more preferably 55° C. to 60° C. Themixture is also kept at this temperature and blended. A suitable way forblending is using an Ultra-Turrax T50 for about 30-60 s at 5000-10000rpm. Subsequently demi-water may be added to this blend, to obtain thedesired dry matter %. A desired dry matter % is for example 15%.Alternatively, the lipid phase is injected to the aqueous phaseimmediately prior to homogenization. It is preferred that injection isperformed immediate before homogenization and under a low pressure inorder to obtain stable large lipid globules.

Minerals, vitamins, and stabilizing gums may be added at various pointsin the process depending on their sensitivity to heat. Mixing can forinstance be performed with a high shear agitator. In the process of thepresent invention, skimmed milk (casein) is preferably not present inthis step and added to the composition after homogenization of the fatfraction into the aqueous fraction (comprising compounds such as whey,whey protein, lactose).

2 Pasteurization

Preferably the mixture is then pasteurized. Pasteurization involves aquick heating step under controlled conditions which microorganismscannot survive. A temperature of 60 to 80° C., more preferably 65 to 75°C., held for at least 15 s, usually adequately reduces vegetative cellsof microorganisms. Several pasteurization methods are known andcommercially feasible. Alternatively this step can also be performedbefore mixing as in step 1 and/or be replaced by the heating step to 60°C. in step 1.

3 Homogenization

Subsequently the optionally pasteurized mixture is homogenized.Homogenization is a process which increases emulsion uniformity andstability by reducing the size of the lipid globules in the formula.This process step can be performed with a variety of mixing equipment,which applies high shear to the product. This type of mixing breaks thelipid globules into smaller globules. The mixture obtained is preferablyhomogenized in two steps at high temperature and pressure, for example60° C. at 30 to 100 and 5 to 50 bar respectively, with a total pressureof 35 to 150 bar. Alternatively, the mixture obtained is preferablyhomogenized in two steps at a lower temperature, between 15 and 40° C.,preferably about 20° C. at 5 to 50 and 5 to 50 bar respectively, with atotal pressure of 5 to 100 bar. In one embodiment, the mixture obtainedis homogenized at 30-100 bar in the first step. In another embodiment,the mixture obtained is homogenized at 5-50 bar in the first step.

This is remarkably lower than standard pressures, which typically are250 to 50 bar, respectively, so a total pressure of 300 bar.

It will be dependent on the specific homogenizer used, which pressure toapply. A suitable way is to use a pressure of 100 bar in the first stepand 50 bar in the second step in a Niro Suavi NS 2006 H Homogenizer at atemperature of 60° C. A suitable way is to use a pressure of 5 bar inthe first step and 20 bar in the second step in a Niro Suavi NS 2006 HHomogenizer at a temperature of 20° C. Subsequently optionally otheringredients, not being lipid, may be added.

4 Sterilization

Subsequently, the emulsion obtained in step 3 is preferably sterilized.Preferably sterilization takes place in-line at ultra high temperature(UHT) and/or in appropriate containers to obtain a formula in the formof a sterile liquid. A suitable way for UHT treatment is a treatment at120-130° C. for at least 20 s. Alternatively, the emulsion obtained instep 3 is concentrated by evaporation, subsequently sterilized at ultrahigh temperature and subsequently spray dried to give a spray driedpowder which is filled into appropriate containers.

Alternatively this sterilization step is performed before thehomogenization step. Preferably the composition obtained by the aboveprocess is spray dried afterwards.

The difference on coating of the lipid globules can further be derivedfrom the zeta potential. Zeta potential (ζ potential) measures thedifference in milliVolts (mV) in electrokinetic potential between thetightly bound layer around the surface and the distant zone ofelectroneutrality and is a measure of the magnitude of the repulsion orattraction between particles in a dispersion. Its value is also relatedto the stability of colloidal dispersions. A high absolute zetapotential will confer stability, i.e. the solution or dispersion willresist aggregation.

Digestible Carbohydrate Component

The composition preferably comprises digestible carbohydrate. Thedigestible carbohydrate preferably provides 30 to 80% of the totalcalories of the composition. Preferably the digestible carbohydrateprovides 40 to 60% of the total calories. When in liquid form, e.g. as aready-to-feed liquid, the composition preferably comprises 3.0 to 30 gdigestible carbohydrate per 100 ml, more preferably 6.0 to 20, even morepreferably 7.0 to 10.0 g per 100 ml. Based on dry weight the presentcomposition preferably comprises 20 to 80 wt. %, more preferably 40 to65 wt. % digestible carbohydrates.

Preferred digestible carbohydrate sources are lactose, glucose, sucrose,fructose, galactose, maltose, starch and maltodextrin. Lactose is themain digestible carbohydrate present in human milk. The presentcomposition preferably comprises lactose. The present compositionpreferably comprises digestible carbohydrate, wherein at least 35 wt. %,more preferably at least 50 wt. %, more preferably at least 75 wt. %,even more preferably at least 90 wt. %, most preferably at least 95 wt.% of the digestible carbohydrate is lactose. Based on dry weight thepresent composition preferably comprises at least 25 wt. % lactose,preferably at least 40 wt. %.

Non-Digestible Oligosaccharides

Preferably the present composition comprises non-digestibleoligosaccharides with a degree of polymerization (DP) between 2 and 250,more preferably 3 and 60. The non-digestible oligosaccharidesadvantageously prevent the onset of insulin resistance, which also willresult in a reduced obesity and/or fat mass later in life. Furthermore,the presence of non-digestible oligosaccharides advantageously resultsin an intestinal microbiota low in Firmicutes and high in Bacteroidetes,which results in a reduced obesity. Therefore the non-digestibleoligosaccharides are presumed to enhance the anti-obesity effects of thelarger lipid globules of the composition according to the presentinvention.

The non-digestible oligosaccharide is preferably selected from the groupconsisting of fructo-oligosaccharides (such as inulin),galacto-oligosaccharides (such as transgalacto-oligosaccharides orbeta-galacto-oligisaccharides), gluco-oligosaccharides (such as gentio-,nigero- and cyclodextrin-oligosaccharides), arabino-oligosaccharides,mannan-oligosaccharides, xylo-oligosaccharides, fuco-oligosaccharides,arabinogalacto-oligosaccharides, glucomanno-oligosaccharides,galactomanno-oligosaccharides, sialic acid comprising oligosaccharidesand uronic acid oligosaccharides. Preferably the composition comprisesgum acacia on combination with a non-digestible oligosaccharide.

Preferably the present composition comprises fructo-oligosaccharides,galacto-oligosaccharides and/or galacturonic acid oligosaccharides, morepreferably galacto-oligosaccharides, most preferablytransgalacto-oligosaccharides. In a preferred embodiment the compositioncomprises a mixture of transgalacto-oligosaccharides andfructo-oligosaccharides. Preferably the present composition comprisesgalacto-oligosaccharides with a DP of 2-10 and/orfructo-oligosaccharides with a DP of 2-60. The galacto-oligosaccharideis preferably selected from the group consisting oftransgalacto-oligosaccharides, lacto-N-tetraose (LNT),lacto-N-neotetraose (neo-LNT), fucosyl-lactose, fucosylated LNT andfucosylated neo-LNT. In a particularly preferred embodiment the presentmethod comprises the administration of transgalacto-oligosaccharides([galactose]_(n)-glucose; wherein n is an integer between 1 and 60, i.e.2, 3, 4, 5, 6, . . . , 59, 60; preferably n is selected from 2, 3, 4, 5,6, 7, 8, 9, or 10). Transgalacto-oligosaccharides (TOS) are for examplesold under the trademark Vivinal™ (Borculo Domo Ingredients,Netherlands). Preferably the saccharides of thetransgalacto-oligosaccharides are β-linked.

Fructo-oligosaccharide is a non-digestible oligosaccharide comprising achain of β linked fructose units with a DP or average DP of 2 to 250,more preferably 10 to 100. Fructo-oligosaccharide includes inulin, levanand/or a mixed type of polyfructan. An especially preferredfructo-oligosaccharide is inulin. Fructo-oligosaccharide suitable foruse in the compositions is also already commercially available, e.g.Raftiline®HP (Orafti).

Uronic acid oligosaccharides are preferably obtained from pectindegradation. Uronic acid oligosaccharides are preferably galacturonicacid oligosaccharides. Hence the present composition preferablycomprises a pectin degradation product with a DP between 2 and 100.Preferably the pectin degradation product is prepared from apple pectin,beet pectin and/or citrus pectin. Preferably the composition comprisestransgalacto-oligosaccharide, fructo-oligosaccharide and a pectindegradation product. The weight ratiotransgalacto-oligosaccharide:fructo-oligosaccharide:pectin degradationproduct is preferably (20 to 2):1:(1 to 3), more preferably (12 to7):1:(1 to 2).

Preferably, the composition comprises of 80 mg to 2 g non-digestibleoligosaccharides per 100 ml, more preferably 150 mg to 1.50 g, even morepreferably 300 mg to 1 g per 100 ml. Based on dry weight, thecomposition preferably comprises 0.25 wt. % to 20 wt. %, more preferably0.5 wt. % to 10 wt. %, even more preferably 1.5 wt. % to 7.5 wt. %. Alower amount of non-digestible oligosaccharides will be less effectivein preventing obesity, whereas a too high amount will result inside-effects of bloating and abdominal discomfort.

Protein Component

The present composition preferably comprises proteins. The proteincomponent preferably provides 5 to 15% of the total calories. Preferablythe present composition comprises a protein component that provides 6 to12% of the total calories. More preferably protein is present in thecomposition below 9% based on calories, more preferably the compositioncomprises between 7.2 and 8.0% protein based on total calories, evenmore preferably between 7.3 and 7.7% based on total calories. A lowprotein concentration advantageously ensures a lower insulin response,thereby preventing proliferation of adipocytes in infants. Human milkcomprises a lower amount of protein based on total calories than cow'smilk. The protein concentration in a nutritional composition isdetermined by the sum of protein, peptides and free amino acids. Basedon dry weight the composition preferably comprises less than 12 wt. %protein, more preferably between 9.6 to 12 wt. %, even more preferably10 to 11 wt. %. Based on a ready-to-drink liquid product the compositionpreferably comprises less than 1.5 g protein per 100 ml, more preferablybetween 1.2 and 1.5 g, even more preferably between 1.25 and 1.35 g.

The source of the protein should be selected in such a way that theminimum requirements for essential amino acid content are met andsatisfactory growth is ensured. Hence protein sources based on cows'milk proteins such as whey, casein and mixtures thereof and proteinsbased on soy, potato or pea are preferred. In case whey proteins areused, the protein source is preferably based on acid whey or sweet whey,whey protein isolate or mixtures thereof and may include α-lactalbuminand β-lactoglobulin. More preferably, the protein source is based onacid whey or sweet whey from which caseino-glyco-macropeptide (CGMP) hasbeen removed. Removal of CGMP from sweet whey protein advantageouslyreduces the threonine content of the sweet whey protein. A reducedthreonine content is also advantageously achieved by using acid whey.Optionally the protein source may be supplemented with free amino acids,such as methionine, histidine, tyrosine, arginine and/or tryptophan inorder to improve the amino acid profile. Preferably α-lactalbuminenriched whey protein is used in order to optimize the amino acidprofile. Using protein sources with an optimized amino acid profilecloser to that of human breast milk enables all essential amino acids tobe provided at reduced protein concentration, below 9% based oncalories, preferably between 7.2 and 8.0% based on calories and stillensure a satisfactory growth. If sweet whey from which CGMP has beenremoved is used as the protein source, it is preferably supplemented byfree arginine in an amount of from 0.1 to 3 wt. % and/or free histidinein an amount of from 0.1 to 1.5 wt. % based on total protein.

Preferably the composition comprises at least 3 wt. % casein based ondry weight. Preferably the casein is intact and/or non-hydrolyzed.

Nutritional Composition

The present composition is preferably particularly suitable forproviding the daily nutritional requirements to a human with an agebelow 36 months, particularly an infant with the age below 24 months,even more preferably an infant with the age below 18 months, mostpreferably below 12 months of age. Hence, the nutritional composition isfor feeding or is used for feeding a human subject. The presentcomposition comprises a lipid, and preferably a protein and preferably adigestible carbohydrate component wherein the lipid component preferablyprovides 30 to 60% of total calories, the protein component preferablyprovides 5 to 20%, more preferably 5 to 15 wt. %, of the total caloriesand the digestible carbohydrate component preferably provides 25 to 75%of the total calories. Preferably the present composition comprises alipid component providing 35 to 50% of the total calories, a proteincomponent provides 6 to 12% of the total calories and a digestiblecarbohydrate component provides 40 to 60% of the total calories. Theamount of total calories is determined by the sum of calories derivedfrom protein, lipids and digestible carbohydrates.

The present composition is not human breast milk. The presentcomposition comprises vegetable lipids. The compositions of theinvention preferably comprise other fractions, such as vitamins,minerals according to international directives for infant formulae.

In one embodiment the composition is a powder suitable for making aliquid composition after reconstitution with an aqueous solution,preferably with water. Preferably the composition is a powder to bereconstituted with water. It was surprisingly found that the size andthe coating with polar lipids of the lipid globules remained the sameafter the drying step and subsequent reconstitution. The presence oflarger lipid globules may have a slightly negative effect on the longterm stability of the liquid composition. However, separation of thelipid and aqueous layers was not observed within 48 h, which is muchlonger than the time between reconstituting the powder to a ready todrink liquid and the consumption of it, which will be less than 24 h andtypically within 1 h. The composition being in a powder form hastherefore an additional advantage in the present invention with largelipid globules.

In order to meet the caloric requirements of the infant, the compositionpreferably comprises 50 to 200 kcal/100 ml liquid, more preferably 60 to90 kcal/100 ml liquid, even more preferably 60 to 75 kcal/100 ml liquid.This caloric density ensures an optimal ratio between water and calorieconsumption. The osmolarity of the present composition is preferablybetween 150 and 420 mOsmol/l, more preferably 260 to 320 mOsmol/l. Thelow osmolarity aims to reduce the gastrointestinal stress. Stress caninduce adipocyte formation.

Preferably the composition is in a liquid form, with a viscosity below35 mPa·s, more preferably below 6 mPa·s as measured in a Brookfieldviscometer at 20° C. at a shear rate of 100 s⁻¹. Suitably, thecomposition is in a powdered from, which can be reconstituted with waterto form a liquid, or in a liquid concentrate form, which should bediluted with water. When the composition is in a liquid form, thepreferred volume administered on a daily basis is in the range of about80 to 2500 ml, more preferably about 450 to 1000 ml per day.

Infant

Adipocytes proliferate during the first 36 months of life as well asmore limited in puberty. The amount of adipocytes is an importantdeterminant in the degree of fat mass, adipose tissue and/or obesitylater-in-life. Hence the present composition is preferably administeredto the human subject during the first 3 years of life. In one embodimentof the use according to the present invention, the nutritionalcomposition is for feeding a human subject with an age between 0 and 36months. It was found that there is a predominance of proliferation ofadipocytes in the first 12 months of life with an optimum in perinataladipocyte proliferation. Hence, it is particularly preferred that thepresent composition is administered to a human subject in this period oflife. The present composition is therefore advantageously administeredto a human of 0-24 months, more preferably to a human of 0-18 months,most preferably to a human of 0-12 months. The present inventionparticularly aims to prevent obesity later-in-life and is preferably notan obesity treatment. Hence, the present composition is preferablyadministered to an infant and/or toddler not suffering from obesity oroverweight. In one embodiment of the use according to the presentinvention, the nutritional composition is for feeding a non-obese humansubject. Preferably the composition is to be used in infants having aweight appropriate for gestational age. Although the adipocyteproliferation is most pronounced during the first 36 months of life andpuberty, adipocytes are formed also to al lesser degree in the intervalbetween 36 months and puberty. So in one embodiment the presentcomposition is preferably administered to an age up to 5 years, morepreferably up to 10 years, more preferably up to 13 years.

Preferably the composition is to be used in infants which areprematurely born or which are small for gestational age. These infantsexperience after birth a catch up growth, which is an extra risk fordeveloping obesity and/or too much fat mass later in life. Preferablythe composition is to be used in infants which are large for gestationalage. These infants have an increased risk of developing obesity and/ortoo much fat mass later in life. Preferably the composition is to beused in infants born from mothers who suffer from obesity and/ordiabetes. Such infants have an increased risk of developing obesityand/or too much fat mass later in life.

Application

The present composition is preferably administered orally to the infant.The present invention also aims to prevent the occurrence of obesityand/or reduce the fat mass at the age above 36 months. In one embodimentthe present method is for preventing obesity, reducing the risk ofobesity and/or for improving body composition of a human subject whensaid human subject has an age above 36 months, preferably when saidhuman subject has an age above 5 years, particularly above 13 years,more particularly above 18 years. In one embodiment the present methodor the present nutritional composition is for feeding a human subjectwith an age between 0 and 36 months and for preventing obesity, reducingthe risk of obesity and/or for improving body composition when saidhuman subject has an age above 36 months, preferably to prevent obesity,reduce the risk of obesity and/or improve body composition at the ageabove 5 years, particularly above 13 years, more particularly above 18years. In one embodiment the prevention of obesity, reduction of therisk of obesity and/or improving of body composition occurs later inlife. With later in life is meant an age exceeding the age at which thediet is taken, preferably exceeding said age with at least one year. Inone embodiment the present method or the present nutritional compositionis for preventing visceral obesity and/or for reducing the ratiovisceral fat to subcutaneous fat.

The inventors surprisingly found that when mice during infancy andchildhood were fed a food composition comprising enlarged lipidglobules, a different and significant effect on body composition laterin life was observed compared to mice which during infancy and childhoodhad been fed a food composition having a similar fatty acid composition,but a smaller lipid globule size. At day 42, which is a time pointcorresponding to childhood in a human setting, no difference wasobserved in growth (weight) between the two groups, but from day 42 bothgroups were fed a Western style diet which was high in fat. Surprisinglyat day 126, which is a time point corresponding to adulthood in humans,the mice, which had previously consumed the food composition of thepresent invention before turning to the Western style diet, had asignificantly lower fat mass and lower relative fat mass than mice whichhad received a control composition. It was in further experimentsdemonstrated that the presence of a coating or outer layer of polarlipids around these dietary lipid globules even further decreased fatmass and relative fat mass compared to large lipid globules without thiscoating. It was also surprisingly found that compared to the controldiet, administering a diet comprising large lipid globules duringinfancy resulted in a specific decrease of visceral fat mass later inlife, i.e. resulted in reduced visceral obesity later in life. This isadvantageous, since in particular visceral obesity is most associatedwith health problems. Furthermore, it was observed that the adipoctehypertrophy was reduced. Obesity caused by adipocyte hypertrophy isthought to be indicative for onset of obesity later in life and is moreassociated with health problems such as insulin resistance than obesitycaused by adipocyte hyperplasia. This is a further indication that thediet does not have an acute effect on treatment or prevention of obesity(which is unwanted in infants) but a programming effect to prevent theoccurrence of obesity later in life.

In this document and in its claims, the verb “to comprise” and itsconjugations is used in its non-limiting sense to mean that itemsfollowing the word are included, but items not specifically mentionedare not excluded. In addition, reference to an element by the indefinitearticle “a” or “an” does not exclude the possibility that more than oneof the element is present, unless the context clearly requires thatthere be one and only one of the elements. The indefinite article “a” or“an” thus usually means “at least one”.

EXAMPLES Example 1 Process for Preparing an IMF with Larger LipidGlobule Size Example 1A

An infant formula was prepared comprising per kg powder 4800 kcal, 248 glipid, 540 g digestible carbohydrates, 55 g non-digestibleoligosaccharides and 103 g protein. The composition was prepared usingBAEF powder (Corman, Goé, Belgium), a vegetable oil blend, demineralisedwhey powder, lactose, non-digestible oligosaccharides(galacto-oligosaccharides and long chain fructo-oligosaccharides in aweight ratio of 9/1). Also vitamins, minerals, trace elements as knownin the art were used.

The amount of BAEF was such that 7.24 wt. % phospholipids (from BAEF)based on total lipids were present in the composition. Based on a smallamounts of phospholipids in the oil blend, the total amount ofphospholipids was 7.39 wt. % based on total lipid. BAEF also supplied asmall amount of cholesterol (about 0.08 wt. % based on total lipid ofthe infant formula) and glycosphingolipids (about 1.65%glycosphingolipids based on total lipid of the infant formula). The BAEFpowder was mixed with galacto-oligosaccharides, lactose, vitaminpre-mixtures and mineral premixes in water, at room temperature, bystiffing. Potassium hydroxide was used to set the pH at 6.8-7.0. The dryweight matter of the mixture was about 27%. The mixture was heated to60° C. The vegetable oil blend was also heated to 60° C. and added tothe water phase and blended with an Ultra-Turrax T50 for about 30-60 sat 5000-10000 rpm. Subsequently demi-water was added to achieve a drymatter content of about 15%.

Subsequently the oil-water mixture was homogenised at a pressure of 100bar in a first step and 50 bar in a second step in a Niro Suavi NS 2006H Homogenizer. The temperature was 60° C. Subsequently demineralizedwhey powder was added to arrive at a final dry matter content of 18%.The product was UHT treated at 125° C. for 30 s. The product was driedto a powder by spray drying. Maltodextrin together with long chaininulin was blended dry into the powder. The size of the lipid globuleswas measured with a Mastersizer 20000 (Malvern Instruments, Malvern UK).The volumetric mode diameter was 7.3 μm. A second, much smaller peak waspresent at 0.52 μm. The volume % of lipid globules with a size between 2and 12 m was 71% based on total lipid volume. It was checked withconfocal laser scanning microscopy that the larger lipid globules of thepresent invention were coated with phospholipids, before spray dryingand after reconstitution of the spray dried powder with water. In bothcases the lipid globules were covered with a layer of phospholipids. Asfluorescent probes Annexin V Alexa Fluor 488 (In Vitrogen molecularprobes) for labeling the phospholipids, and Nile Red (Sigma-Aldrich) forlabeling triglycerides, were used. After labeling the milk samplesVectrahield mounting medium (Vector laboratories inc., Burliname USA)for reducing particle movement and photo-bleaching was added.Observations were made using a Zeiss Laser Scanning Microscope withexcitation wavelengths of 488/543/633 nm and emission filters set atband pass 505-530, and band pass 560-615. Also the size of the lipidglobules was the same before drying and after reconstitution of thespray dried powder with water.

As a control the lipid globules of a standard infant formula(Nutrilon 1) did not show labeling with phospholipids as observed withthe confocal laser scanning microscopy. Instead the globules werecovered with protein, as determined with the fluorescent protein stainFast Green FCF. The volumetric modal diameter of the lipid globules inthis standard infant milk formula was measured to be 0.5 μm. A secondmuch smaller peak was present at 8.1 μm. The volume % of lipid globuleswith a size between 2 and 12 m was 34% based on total lipid volume.

TABLE 1 Lipid globule characteristics of different milks Volume Volume %with a Mode diameter diameter between ζ potential μm 2 and 12 μm (mV)Standard infant 0.5 34 −22.4 milk formula (Nutrilon 1) Infant milk 7.371 −16 formula of the invention Human milk 5.3 98 −13.8

Also human milk was analyzed and showed a volumetric modal diameter ofthe lipid globules of 5.3 μm. The volume % of lipid globules with a sizebetween 2 and 12 m was 98% based on total lipid volume. The lipidglobules were covered with a layer of phospholipids.

The zeta potentials and volume weighted mean diameters were alsomeasured. The results are shown in table 1.

Example 1B

Infant formula were prepared similar to example 1A. The oil blend wasprepared using vegetable oils, oil soluble vitamins and antioxidants.Both the water phase and the oil blend were heated to 65° C. prior tomixing. The oil blend was added to the water phase and blended with anUltra-Turrax T50 for about 30-60 s at 5000-1000 rpm. The dry weight ofthis mixture was about 26%. The product was UHT treated for 30 s at 125°C. and subsequently cooled to 20° C.

For diet 2 and 3 and 4 this mixture was homogenized in two steps at apressure of 5 and 20 bar respectively in a Niro Suavi NS 2006 Hhomogenizer. For diet 1 the homogenization pressure was 200 and 50 bar,respectively in a Niro Suavi NS 2006 H homogenizer. The products weredried to a powder by spray drying. Long chain inulin was blended dryinto the powder. For diet 1 and 2 no added polar lipids were present.The amount of vegetable glycerophospholipids was 0.2 wt. % based ontotal fat for diet 1 and 2. Diet 1 and 2 did not contain sphingolipidsand cholesterol. For diet 3 and 4 a butter milk powder was used. Diet 3comprised 1.83 wt. % glycerophospholipids based on total fat, of whichabout 90% derived from the butter milk powder and about 10% alreadypresent in the standard IMF derived from vegetable oils, and furthercomprised milk derived sphingolipids of which the majority (about 0.47wt. % based on total fat) was sphingomyelin; the rest beingglycosphingolipids, of which the majority (over 60%) is GD3 with aconcentration of about 0.13 wt. % based on total fat. Diet 3 comprisedabout 0.05 wt. % milk derived cholesterol based on total fat. Diet 4comprised half of the amount of milk derived polar lipids based on totalfat of diet 3.

In diet 3 the butter milks powder comprising these polar lipids were dryblended after the homogenization, sterilization and spray dry step inorder to prevent coating of the lipid globules.

In diet 4 the butter polar lipids were present in the aqueous phaseduring the homogenization step in order to coat the lipid globules.

The size of the lipid globules was measured with a Mastersizer 20000(Malvern Instruments, Malvern UK) and shown in Table 2. Coating of thelipid globules with polar lipids in diet 4 and absence of coating indiet 1, 2 and 3 was confirmed by the confocal laser scanning microscopymethod as described above.

TABLE 2 Lipid globule characteristics of different milks Volume ModeVolume % with a diameter IMF diameter μm between 2 and 12 μm 1, StandardIMF 0.5 5.1 2, Experimental IMF (large 4.0 72.2 lipid globules) 3,Experimental IMF (large 5.0 74.8 lipid globules, free polar lipids) 4,Experimental IMF (large 4.3 70.3 lipid globules coated with polarlipids)

After 5 months storage at room temperature the size of the lipidglobules in diet 1 had not changed, with a volume mode diameter of 0.5.Also the volume mode diameter of diet 2, 3 and 4 were rather stablebeing 4.8 μm, 7.9 μm and 6.6 μm respectively.

Example 2 Programming Effect of Lipid Globule Size on Adult BodyComposition

Offspring of C57/BL6 dams were weaned from day 15 on. The experimentalweaning diets were continued until day 42. From day 42 to day 126 allpups were fed the same diet based on AIN-93G diet with an adjusted lipidfraction (containing 10 wt. % lipid of which 50 wt. % lard and 1%cholesterol, based on total lipid), which is representative for aWestern style diet.

The experimental diets that were used for weaning were:

1) an infant milk formula (IMF) based control diet. This diet comprised282 g standard IMF (Nutrilon 1) per kg, with the lipid globule size asmentioned in example 1A. The rest of the diet was AIN-93G protein,carbohydrates and fibre. All lipid present in the diet was derived fromthe IMF.

2) an IMF based diet of the present invention. This diet differed fromdiet 1 in that it comprised 282 g IMF of example 1A, i.e. comprisedlipid globules larger than the control. All lipid present in the dietwas derived from the IMF.

At day 42, all mice switched to a “Western style diet” comprising 10 wt.% lipid until day 126. The composition of the diets is given in table 3.The fatty acid composition of the two experimental and cafeteria diet isshown in table 4. The fatty acid profile of the two experimental dietswas very similar.

TABLE 3 composition of experimental diets per kg Diet 1, Diet 2, IMFWestern style Control IMF of the invention diet Kcal 3922 3922 4016Lipid (g) 70 70 100 Phospholipids (g) 0.12 5.16 n.d. Cholesterol (g)0.00 0.06 1 Digestible 644 644 600 Carbohydrates (g) Lactose (g) 145.9145.9 0 Sucrose, glucose (g) 85 85 150 Maltodextrin (g) 360 360 450Fiber (g) 47.5 47.5 47.5 Protein 179 179 179 n.d. = not determined

The mice were weighed twice a week. The food intake was determined oncea week during the entire experiment. To determine body composition(i.e., fat mass (FM) and fat-free mass (FFM)) DEXA scans (Dual EnergyX-ray Absorbiometry) were performed under general anesthesia at 6, 10and 14 weeks of age, 42, 70, 98 and 126 days after birth respectively,by densitometry using a PIXImus imager (GE Lunar, Madison, Wis., USA).At the age of 126 days the male mice were sacrificed and organs weredissected and weighed (i.e. fat tissues, liver, Muscle tibialis). Bloodwas analyzed for leptin, resistin, and (fasting) insulin.

TABLE 4 Fatty acid composition of the experimental diets Diet 1, Diet 2,IMF of Western Control IMF the invention style diet C12:0 9.4 8.7 5.3C14:0 4.4 5.3 2.7 C16:0 18.7 21.3 23.1 C18:0 3.5 5.2 9.0 C18:1 n-9 39.937.7 40.5 C18:2 n-6 (LA) 15.7 12.6 11.9 C18:3 n-3 (ALA) 2.4 2.1 1.3Others 6.0 7.1 6.7 n-6 16.0 12.9 11.9 n-3 2.4 2.1 1.3 n-6/n-3 6.58 6.129.1 LA/ALA 6.46 6.00 9.15 SFA 39.3 44.4 41.9 MFA 42.1 39.8 42.3 PUFA18.3 14.9 13.2Results:

No effect on growth (body weight) and food intake was observed duringthe experimental period between the groups. Moreover, the development offat mass (determined with DEXA) was not significantly different at day42 (end of the diet intervention period).

A subsequent treatment with a Western style diet between day 42 and day126 of all groups resulted in clear differences in body composition atthe end of the experiment (day 126), see Table 5. The fat mass andrelative fat mass developed later in life was reduced in the pups whichhad received the diet with the larger lipid globules during theirinfancy and childhood, compared to pups which had received the controldiet. The overall body weight was comparable between the two groups. Theexperimental group had an increased lean body mass.

TABLE 5 Body weight, lean body mass, fat mass and relative fat mass.Diet 2, IMF of the Parameter Day Diet 1, Control IMF inventionBodyweight g 42 23.50 (0.45) 24.24 (0.51) Mean (s.e.) 70 29.88 (0.46)30.16 (0.77) 98 33.32 (0.57) 33.69 (0.95) 126 34.47 (0.80) 34.15 (1.16)Lean body mass g 42 18.96 (0.34) 19.96 (0.40)* Mean (s.e.) 70 21.31(0.42) 22.32 (0.48) 98 22.22 (0.49) 23.91 (0.45)* 126 23.30 (0.43) 24.19(0.53)* Fat mass g 42  3.78 (0.13)  3.77 (0.21) Mean (s.e.) 70  7.84(0.35)  7.13 (0.65) 98 10.68 (0.53)  9.19 (0.79)* 126 10.48 (0.67)  9.11(0.90)* Fat % of body weight 42 16.59 (0.45) 15.83 (0.68) Mean (s.e.) 7026.89 (1.07) 23.81 (1.61) 98 32.38 (1.42) 27.25 (1.67)* 126 30.78 (1.42)26.67 (1.77)* *P < 0.05 compared to control group

The liver in the control group had a mean weight of 157 g (s.e. 0.07)and in the experimental diet 1.44 g (s.e. 0.15). This is indicative fora reduced fatty liver in the experimental group. The Muscle tibialis was95.3 g (mean, with s.e. 2.1) in the control group and 96.7 g (s.e. 3.2)in the experimental group. This corresponds with the effects on leanbody mass. The effects on fat tissues is shown in Table 6. In theexperimental group the animals showed a higher amount of brown adiposetissue (BAT), but lower amounts of white adipose tissues (WAT), such asthe retroperitoneal (rp), inguinal (i) and epididymal (e) fat. Thepresence of brown adipose tissue is advantageous for infants forinsulation purposes. White adipose tissue is present in adults as wellas infants and is used for energy storage. Lower visceral fat mass (i.e.eWAT and rpWAT) is also advantageous, since it will decrease the risk ofinsulin insensitivity or insulin resistance.

TABLE 6 Adipose tissue mass in mice on day 126. Diet 1, Diet 2, IMF ofFat tissue Control IMF the invention BAT mg mean (s.e.) 150.0 (9.0)180.4 (16.5) rpWAT mg mean (s.e.) 379.0 (31.6) 349.3 (35.5) iWAT mg mean(s.e.) 772.3 (43.9) 665.5 (50.5) eWAT mg mean (s.e.)  1380 (100)  1300(130)

Fasting insulin levels were lower in the experimental group (1200 units)than in the control group (1470 units). This is indicative for a reducedadipocyte signal. Leptin levels were decreased in the experimental group(6000 units) compared to the control group (9500). Resistin was alsodecreased in the experimental group (1350) compared to the control group(1550). This is indicative for a normal appetite and a reduced tendencyfor adiposity, i.e. increased fat mass, respectively.

These results demonstrate that the fat mass, relative fat mass and/orobesity in later life clearly is decreased by an early in life diet withincreased lipid globule size. It is concluded that food comprising lipidglobules with an altered lipid architecture program and/or imprint thebody early in life in such a way that later in life a healthier bodycomposition develops, with less fat mass, relative fat mass and/or withincreased lean body mass.

Example 3 Programming Effect of Lipid Globule Size on Adult BodyComposition

The same experimental animal model and set up was used as in example 2,except that the experiment was terminated at day 98 instead of day 128.

The experimental diets that were used for weaning were:

1) an infant milk formula (IMF) based control diet. This diet comprised282 g standard IMF per kg, IMF 1 of example 1B, i.e. small lipidglobules, and no added polar lipids. The rest of the diet was AIN-93Gprotein, carbohydrates and fibre. All lipid present in the diet wasderived from the IMF.

2) an IMF based diet of the present invention. This diet differed fromdiet 1 in that it comprised 282 g IMF 2 of example 1B, i.e. comprisedlipid globules larger than the control and no added polar lipids. Alllipid present in the diet was derived from the IMF.

3) an IMF based diet of the present invention with added phospholipids.This diet differed from diet 2 in that it comprised 282 g IMF 3 ofexample 1B, i.e. comprised lipid globules larger than the control andadded polar lipids, not located at the outer surface layer of the lipidglobule. All lipid present in the diet was derived from the IMF.

4) an IMF based diet of the present invention. This diet differed fromdiet 3 in that it comprised 282 g IMF 4 of example 1B, i.e. comprisedlipid globules larger than the control coated with polar lipids derivedfrom milk. All lipid present in the diet was derived from the IMF.

The composition of the diets is similar as in table 3 of example 2. Thefatty acid composition of the two experimental and cafeteria diet issimilar as in table 4 of example 2, with calculated linoleic acid (LA)of 14% in diet 1 and 2 and 13.2% in diet 3 and 4 based on total fattyacids, with alpha linoleinc acid (ALA) of 2.6 in diet 1 and 2 and 2.5.%in diet 3 and 4 based on total fatty acids and with LA/ALA of 5.4 indiet 1 and 2 and 5.3, in diet 3 and 4 respectively. The amount of DHAwas 0.2 wt. % in all 4 diets, and the amount of ARA was 0.35 wt. % indiet 1 and 2 and 0.36 wt. % in diet 3 and 4.

Results:

No effect on growth (body weight) and food intake was observed duringthe experimental period between the groups. Moreover, the development ofbody weight and fat mass (determined with DEXA) was not significantlydifferent at day 42 (end of the diet intervention period).

A subsequent treatment with a Western style diet between day 42 and day98 of all groups resulted in clear differences in body composition atthe end of the experiment (day 98), see Table 7. The fat mass andrelative fat mass developed later in life was reduced in the mice whichhad received the diet with the larger lipid globules during theirinfancy and childhood, compared to mice which had received the controldiet.

TABLE 7 Fat mass and relative fat mass. Parameter Day Diet 1 Diet 2 Diet3 Diet 4 Fat mass g 98 8.35 (0.67) 7.29 (0.37) 7.93 (0.52) 6.43 (0.66)*Mean (s.e.) Delta 98-42 3.93 (0.61) 3.10 (0.39) 3.96 (0.58) 2.40 (0.68)*Fat % of body 98 26.31 (1.33)  24.18 (0.83)  25.48 (1.19)  22.48(1.29)*  weight Delta 98-42 8.88 (1.28) 7.21 (0.83) 9.42 (1.23) 5.93(1.44)* Mean (s.e.) *P < 0.05

From the results above it can be deduced that increase in size of lipidglobule results in decreased fat mass and relative fat mass (comparediet 1 versus diet 2). The decrease in fat mass and relative fat mass iseven higher when the lipid globules are coated with polar lipids derivedfrom milk lipids (compare diet 4 with diet 1 or 2). This improved effectis considered not only to be due to the polar lipids it itself, but canpossibly also be attributed to the coating of the lipid globules, sincewith diet 3 the effects are much less pronounced as in with diet 4.

TABLE 8 Adipose tissue mass in mice on day 98. Fat tissue Diet 1 Diet 2Diet 3 Diet 4 iWAT* mean 520 (40) 550 (40) 500 (30) 410 (30) (s.e.)periWAT mean 64 (8) 41 (5) 57 (7) 47 (6) (s.e.) Rp WAT mean 280 (30) 280(20) 270 (20) 230 (30) (s.e.) eWAT mean 1070 (110) 1010 (70)  980 (80) 870 (110) (s.e.) iWAT/ 1.51 1.71 1.53 1.48 (periWAT + rpWAT) *WAT:white adipose tissue i: inguinal rp: retroperitoneal peri: perirenal e:epididymal

The effect on fat tissues is shown in Table 8. Larger lipid globulesresulted especially in decreased visceral fat (perirenal fat andepididymal fat) compared to subcutaneous fat (compare diet 1 with diet2).

White adipose tissue is present in adults as well as infants and is usedfor energy storage. Lower visceral fat mass (i.e. eWAT and rpWAT) isadvantageous, since it will decrease the risk of insulin insensitivityor insulin resistance.

In the adipose tissues (eWAT and iWAT) of mice fed with diet 1 and diet4 the cell size was determined at day 98. Adipocytes were isolated andthe mean diameter was determined by image analysis of microscopicpictures. The volume was calculated as V=(π/6)(3σ+X²)X where X and σ²are the mean and the variance of the diameter. The mean volume ofadipocytes in eWAT, representative of visceral fat, of mice fed withdiet 1 was 5.1 10⁶ μm³ (s.e. 0.56 10⁶) and of mice fed diet 4 was 4.310⁶ μm³ (s.e. 0.52 10⁶). The mean volume of adipocytes in iWAT,representative of subcutaneous fat, was less. In mice fed with diet 1 itwas 2.0 10⁶ μm³ (s.e. 0.16 10⁶) and of mice fed diet 4 was 1.7 10⁶ μm³(s.e. 0.1.4 10⁶). The number of cells was slightly higher in the diet 4fed mice. No differences were observed in % lipid content and lipiddensity of the adipose fat mass.

These results demonstrate that the fat mass, relative fat mass and/orobesity in later life clearly is decreased by an early in life diet withincreased lipid globule size. These effects are even more pronouncedwhen the large lipid globules are coated with polar lipids. Furthermore,larger lipid globules resulted in a specific effect in reducing visceralobesity. It is concluded that food comprising lipid globules with analtered lipid architecture program and/or imprint the body early in lifein such a way that later in life during growth under similarcircumstances a healthier body composition develops, with less fat mass,and/or relative fat mass.

Example 4 Infant Nutrition with Larger Lipid Globules Size

An infant formula comprising per kg powder 4810 kcal, 255 g lipid, 533 gdigestible carbohydrates, 58 g non-digestible oligosaccharides(galacto-oligosaccharides and long chain fructo-oligosaccharides in aweight ratio of 9/1), 96 g protein, and vitamins, minerals, traceelements as known in the art.

The lipid composition is such that 0.57 wt. % of the lipid is composedof phospholipids. The composition comprises about 0.17 wt. %glycosphingolipids based on total lipid. The composition comprises about0.006 wt. % cholesterol based on total lipids. As a source ofphospholipids, glycosphingolipids and cholesterol SM-2 powder (Corman,Goé, Belgium) is used. About 97-98% of the lipid is vegetable lipid, therest being milk fat, fish oil and microbial oil. The amount of LC-PUFAis about 0.64 wt. % based on total fatty acids. The LA/ALA ratio is 5.2.

Homogenization was performed similar as in example 1. The volumetricmode diameter was above 1 μm. The volume % of lipid globules with a sizebetween 2 and 12 m was above 45% based on total lipid volume.

The invention claimed is:
 1. A method of preventing, reducing and ortreating obesity, comprising administering to a human subject between 0and 36 months of age and in need thereof a nutritional compositioncomprising: (i) 10 to 50 wt. % vegetable lipids based on dry weight ofthe composition, and polar lipids selected from a) 0.3 to 25 wt. % polarlipids based on total lipids, wherein polar lipids are the sum ofphospholipids, glycosphingolipids and cholesterol, or b) 0.2 to 20 wt. %phospholipids, based on total lipids, and (ii) lipid globules having (a)a volume-weighted mode diameter above 1.0 μm, and/or (b) a diameter of 2to 12 μm in an amount of at least 45 volume % based on total lipid;wherein the lipid globules are coated with phospholipids.
 2. The methodof claim 1, wherein the lipid globules have a volume-weighted modediameter between 1.0 and 10 μm.
 3. The method according to claim 1,wherein the lipid globules have a diameter of 2 to 12 μm in an amount ofat least 55 volume % based on total lipid.
 4. The method according toclaim 1, wherein the subject is a human subject 36 months of age orolder.
 5. The method according to claim 1, wherein the subject is ahuman subject above 5 years of age.
 6. The method according to claim 1,wherein the subject is a non-obese human subject.
 7. The methodaccording to claim 1, wherein the obesity is visceral obesity.
 8. Themethod according to claim 1, wherein the lean body mass of the subjectis increased, fat mass of the subject is decreased, and/or fat massrelative to total body weight of the subject is decreased.
 9. The methodaccording to claim 1, wherein the composition further comprises 0.6 to25 wt. % polar lipids based on total lipid, wherein the polar lipids arethe sum of phospholipids, glycosphingolipids, and cholesterol.
 10. Themethod according to claim 1, wherein the lipid globules are coated witha layer of phospholipids and polar lipids.
 11. The method according toclaim 1, wherein the composition has a fatty acid profile with alinoleic acid to alpha-linolenic acid weight ratio between 4 and
 7. 12.The method according to claim 1, wherein the composition furthercomprises at least one lipid selected from the group consisting of fishoil, marine oil, algal oil, fungal oil and microbial oil.
 13. The methodaccording to claim 1, wherein the composition further comprises 6 to 12%protein based on total calories.
 14. The method according to claim 1,wherein the composition further comprises non-digestibleoligosaccharides.
 15. The method according to claim 1, wherein thecomposition is in the form of a powder.